Genetic techniques allow the identification of single nucleotide polymorphisms (SNPs) in individuals. SNPs are changes in a gene in one single nucleotide. Identification of SNPs can be correlated with a biological pathway having implications for a particular disease. The polymorphisms may be correlated also with a predisposition or risk for a disease by application of statistical analyses. Accordingly, targeting a particular biological pathway related to a disease is a means to treat such disease.
B-cell scaffold protein with ankyrin repeats (BANK1) is expressed in B cells and is tyrosine phosphorylated upon B-cell antigen receptor (BCR) stimulation. The BANK1 gene has 284 kb. BANK1 is an adaptor protein (6, 7) expressed mainly in B cells. The two full length isoforms of 785 and 755 amino acids, differ by 30 amino acids in the N-terminal region coded by the alternative exon 1A (FIG. 1e) and contain ankyrin repeat motifs and coiled-coil regions—structures highly similar between BANK1, BCAP and D of adaptor proteins (8). B cell activation through BCR engagement leads to tyrosine phosphorylation of BANK1, which in turn promotes its association with the protein tyrosine kinase Lyn and the calcium channel IP3R (3). BANK1 serves as a docking station bridging together and facilitating phosphorylation and activation of IP3R by Lyn and the consequent release of Ca2+ from endoplasmic reticulum stores (3, 9). It was previously found that IP3R associates with the SNP rs10516487 lying within a region essential for binding of IP3R.
The BANK1 SNPs rs17266594 and rs3733197 have also been described in the literature.
None of the above SNPs have been described in the literature to be useful for the prediction of an inflammatory, auto-immune or neurological disease.
BANK1 and the pathway it is involved in, is considered to have implications for inflammatory and auto-immune disorders. In particularly, BANK1 is expressed in B-cells and therefore the pathway wherein BANK1 is involved has an implication for diseases associated with B-cells, e.g. Systemic Lupus Erythematosus (SLE). Multiple Sclerosis (MS) is related to T-cells, however, also the role of B-cells has been discussed in this disease. Accordingly, polymorphisms in the BANK1 gene may be used to diagnose a predisposition or risk for MS. Moreover, the BANK1 pathway may have implications for MS. In consequence, targeting this pathway and its modulation may represent a means to prevent or treat MS.